title: Quinolone prophylaxis for the prevention of BK virus infection in kidney transplantation: study protocol for a randomized controlled trial.
abstract: BACKGROUND
  BK virus infection has emerged as a major complication in kidney transplantation leading to a significant reduction in graft survival. There are currently no proven strategies to prevent or treat BK virus infection. Quinolone antibiotics, such as levofloxacin, have demonstrated activity against BK virus. We hypothesize that administration of a quinolone antibiotic, when given early post-transplantation, will prevent the establishment of BK viral replication in the urine and thus prevent systemic BK virus infection.
  
  
  METHODS
  The aim of this pilot trial is to assess the efficacy, safety and feasibility of a 3-month course of levofloxacin in the kidney transplant population. This is a multicenter, randomized, double-blind, placebo-controlled trial with two parallel arms conducted in 11 Canadian kidney transplant centers. A total of 154 patients with end-stage renal disease undergoing kidney transplantation will be randomized to receive a 3-month course of levofloxacin or placebo starting in the early post-transplant period. Levofloxacin will be administered at 500 mg po daily with dose adjustments based on kidney function. The primary outcome will be the time to occurrence of BK viruria within the first year post-transplantation. Secondary outcomes include BK viremia, measures of safety (adverse events, resistant infections,Clostridium difficile-associated diarrhea), measures of feasibility (proportion of transplanted patients recruited into the trial), proportion of patients adherent to the protocol, patient drop-out and loss to follow-up,and use of quinolone antibiotics outside of the trial protocol.
  
  
  CONCLUSIONS
  Results from this pilot study will provide vital information to design and conduct a large, multicenter trial to determine if quinolone therapy decreases clinically meaningful outcomes in kidney transplantation. If levofloxacin significantly reduces BK viruria and urine viral loads in kidney transplantation, it will provide important justification to progress to the larger trial. If the full trial shows that levofloxacin significantly reduces BK infection and improves outcomes, its use in kidney transplantation will be strongly endorsed given the lack of proven therapies for this condition.
  
  
  BACKGROUND
  This trial was funded by the Canadian Institutes of Health Research (grant number:222493) and is registered at ClinicalTrials.gov (NCT01353339).
authors.affiliation: Department of Medicine, Faculty of Medicine & Dentistry, 2J2.00 WC Mackenzie Health Sciences Centre, University of Alberta, Edmonton, AB T6G 2R7, Canada.
authors.forename: Atul
authors.initials: A
authors.lastname: Humar
authors.forename: John
authors.initials: J
authors.lastname: Gill
authors.forename: Olwyn
authors.initials: O
authors.lastname: Johnston
authors.forename: Dean
authors.initials: D
authors.lastname: Fergusson
authors.forename: Andrew A
authors.initials: AA
authors.lastname: House
authors.forename: Louise
authors.initials: L
authors.lastname: Lebel
authors.forename: Sandra
authors.initials: S
authors.lastname: Cockfield
authors.forename: S Joseph
authors.initials: SJ
authors.lastname: Kim
authors.forename: Jeff
authors.initials: J
authors.lastname: Zaltzman
authors.forename: Marcelo
authors.initials: M
authors.lastname: Cantarovich
authors.forename: Martin
authors.initials: M
authors.lastname: Karpinski
authors.forename: Tim
authors.initials: T
authors.lastname: Ramsay
authors.forename: Greg A
authors.initials: GA
authors.lastname: Knoll
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects; D019072:Antibiotic Prophylaxis; D001739:BK Virus / Q000472:pathogenicity*; D002170:Canada; D002985:Clinical Protocols; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D006801:Humans; D007676:Kidney Failure, Chronic / Q000601:surgery*; D016030:Kidney Transplantation / Q000009:adverse effects*; D064704:Levofloxacin; D015242:Ofloxacin / Q000008:administration & dosage* / Q000009:adverse effects; D010865:Pilot Projects; D027601:Polyomavirus Infections / Q000175:diagnosis / Q000517:prevention & control* / Q000821:virology; D012107:Research Design; D013997:Time Factors; D016896:Treatment Outcome; D014412:Tumor Virus Infections / Q000175:diagnosis / Q000517:prevention & control* / Q000821:virology
chemical_list: D000900:Anti-Bacterial Agents; D064704:Levofloxacin; D015242:Ofloxacin